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CYP2C19 genetic mutations in North Indians
Objectives To identify defective alleles of CYP2C19 (CYP2C19*2 and *3) in North Indians. Methods One hundred extensive metabolizers and 21 poor metabolizers of omeprazole were genotyped with respect to CYP2C19*2 and *3 alleles with polymerase chain reaction–based diagnostic tests. Results Fifty‐two...
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| Published in: | Clinical pharmacology and therapeutics 2000-09, Vol.68 (3), p.328-335 |
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| container_title | Clinical pharmacology and therapeutics |
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| creator | Lamba, Jatinder K. Dhiman, Radha K. Kohli, Krishan K. |
| description | Objectives
To identify defective alleles of CYP2C19 (CYP2C19*2 and *3) in North Indians.
Methods
One hundred extensive metabolizers and 21 poor metabolizers of omeprazole were genotyped with respect to CYP2C19*2 and *3 alleles with polymerase chain reaction–based diagnostic tests.
Results
Fifty‐two extensive metabolizers and six poor metabolizers were homozygous with the CYP2C19*1 /*1 genotype, and 48 extensive metabolizers and six poor metabolizers were heterozygous with the CYP2C19*1/*2 genotype. Nine poor metabolizers were homozygous with the CYP2C19*2/*2 genotype. No extensive or poor metabolizers demonstrated the presence of the CYP2C19*3 allele. CYP2C19*2 could explain 43% (9/21) of the poor metabolizers and 57% (24/42) of the defective alleles in poor metabolizers. Allele frequency of CYP2C19*1 and *2 was 0.7 (95% confidence interval of 0.65 to 0.75) and 0.3 (95% confidence interval of 0.25 to 0.35), respectively. Homozygous extensive metabolizers excreted 7.85 ± 7.6 μmol 5‐hydroxyomeprazole in 8 hours, which was 28% more as compared with heterozygous extensive metabolizers who excreted 5.6 ± 3.6 μmol 5‐hydroxyomeprazole in 8 hours (P < .05).
Conclusions
Cyp2C19*2 demonstrated allele frequency of 0.3, whereas CYP2C19*3 was absent in North Indians. Because CYP2C19*2 is not able to explain 57% of poor metabolizers, other mutations (CYP2C19*4 to *8) might be present in North Indians. CYP2C19 demonstrated differential evolution in North Indians because the frequency of CYP2C19*2 was similar to that in Oriental subjects, but that of CYP2C19*3 was similar to that in white subjects.
Clinical Pharmacology & Therapeutics (2000) 68, 328–335; doi: 10.1067/mcp.2000.109365 |
| doi_str_mv | 10.1067/mcp.2000.109365 |
| format | article |
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To identify defective alleles of CYP2C19 (CYP2C19*2 and *3) in North Indians.
Methods
One hundred extensive metabolizers and 21 poor metabolizers of omeprazole were genotyped with respect to CYP2C19*2 and *3 alleles with polymerase chain reaction–based diagnostic tests.
Results
Fifty‐two extensive metabolizers and six poor metabolizers were homozygous with the CYP2C19*1 /*1 genotype, and 48 extensive metabolizers and six poor metabolizers were heterozygous with the CYP2C19*1/*2 genotype. Nine poor metabolizers were homozygous with the CYP2C19*2/*2 genotype. No extensive or poor metabolizers demonstrated the presence of the CYP2C19*3 allele. CYP2C19*2 could explain 43% (9/21) of the poor metabolizers and 57% (24/42) of the defective alleles in poor metabolizers. Allele frequency of CYP2C19*1 and *2 was 0.7 (95% confidence interval of 0.65 to 0.75) and 0.3 (95% confidence interval of 0.25 to 0.35), respectively. Homozygous extensive metabolizers excreted 7.85 ± 7.6 μmol 5‐hydroxyomeprazole in 8 hours, which was 28% more as compared with heterozygous extensive metabolizers who excreted 5.6 ± 3.6 μmol 5‐hydroxyomeprazole in 8 hours (P < .05).
Conclusions
Cyp2C19*2 demonstrated allele frequency of 0.3, whereas CYP2C19*3 was absent in North Indians. Because CYP2C19*2 is not able to explain 57% of poor metabolizers, other mutations (CYP2C19*4 to *8) might be present in North Indians. CYP2C19 demonstrated differential evolution in North Indians because the frequency of CYP2C19*2 was similar to that in Oriental subjects, but that of CYP2C19*3 was similar to that in white subjects.
Clinical Pharmacology & Therapeutics (2000) 68, 328–335; doi: 10.1067/mcp.2000.109365</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1067/mcp.2000.109365</identifier><identifier>PMID: 11014415</identifier><identifier>CODEN: CLPTAT</identifier><language>eng</language><publisher>New York, NY: Nature Publishing</publisher><subject>Alleles ; Antisense Elements (Genetics) ; Aryl Hydrocarbon Hydroxylases ; Biological and medical sciences ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 Enzyme System - genetics ; Female ; General pharmacology ; Genetics, Population ; Genotype ; Humans ; India ; Male ; Medical sciences ; Mixed Function Oxygenases - genetics ; Omeprazole - metabolism ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Genetic</subject><ispartof>Clinical pharmacology and therapeutics, 2000-09, Vol.68 (3), p.328-335</ispartof><rights>2000 American Society for Clinical Pharmacology and Therapeutics</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3062-146a29651efb5926ce04153196bd4ea0e6e2ad72171ef2f0c0d3652f82c4c6a13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1500485$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11014415$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lamba, Jatinder K.</creatorcontrib><creatorcontrib>Dhiman, Radha K.</creatorcontrib><creatorcontrib>Kohli, Krishan K.</creatorcontrib><title>CYP2C19 genetic mutations in North Indians</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>Objectives
To identify defective alleles of CYP2C19 (CYP2C19*2 and *3) in North Indians.
Methods
One hundred extensive metabolizers and 21 poor metabolizers of omeprazole were genotyped with respect to CYP2C19*2 and *3 alleles with polymerase chain reaction–based diagnostic tests.
Results
Fifty‐two extensive metabolizers and six poor metabolizers were homozygous with the CYP2C19*1 /*1 genotype, and 48 extensive metabolizers and six poor metabolizers were heterozygous with the CYP2C19*1/*2 genotype. Nine poor metabolizers were homozygous with the CYP2C19*2/*2 genotype. No extensive or poor metabolizers demonstrated the presence of the CYP2C19*3 allele. CYP2C19*2 could explain 43% (9/21) of the poor metabolizers and 57% (24/42) of the defective alleles in poor metabolizers. Allele frequency of CYP2C19*1 and *2 was 0.7 (95% confidence interval of 0.65 to 0.75) and 0.3 (95% confidence interval of 0.25 to 0.35), respectively. Homozygous extensive metabolizers excreted 7.85 ± 7.6 μmol 5‐hydroxyomeprazole in 8 hours, which was 28% more as compared with heterozygous extensive metabolizers who excreted 5.6 ± 3.6 μmol 5‐hydroxyomeprazole in 8 hours (P < .05).
Conclusions
Cyp2C19*2 demonstrated allele frequency of 0.3, whereas CYP2C19*3 was absent in North Indians. Because CYP2C19*2 is not able to explain 57% of poor metabolizers, other mutations (CYP2C19*4 to *8) might be present in North Indians. CYP2C19 demonstrated differential evolution in North Indians because the frequency of CYP2C19*2 was similar to that in Oriental subjects, but that of CYP2C19*3 was similar to that in white subjects.
Clinical Pharmacology & Therapeutics (2000) 68, 328–335; doi: 10.1067/mcp.2000.109365</description><subject>Alleles</subject><subject>Antisense Elements (Genetics)</subject><subject>Aryl Hydrocarbon Hydroxylases</subject><subject>Biological and medical sciences</subject><subject>Cytochrome P-450 CYP2C19</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Female</subject><subject>General pharmacology</subject><subject>Genetics, Population</subject><subject>Genotype</subject><subject>Humans</subject><subject>India</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mixed Function Oxygenases - genetics</subject><subject>Omeprazole - metabolism</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><recordid>eNqFkM1LwzAUwIMobk7P3qQH8SB0y0uatMHTKH4Mhu4wD55ClqYa6cdsWmT_vSkt7OgpvLzf-_ohdA14DpjHi1Lv5wTjPhKUsxM0BUZJyBllp2jqEyIUhPIJunDu24eRSJJzNAHAEEXApug-_diQFETwaSrTWh2UXataW1cusFXwWjftV7CqMqsqd4nOclU4czW-M_T-9LhNX8L12_MqXa5DTTEnIURcEcEZmHzHBOHaYD-JguC7LDIKG26IymICsSdIjjXO_OYkT4iONFdAZ-hu6Ltv6p_OuFaW1mlTFKoydedkTCj2xzMPLgZQN7VzjcnlvrGlag4SsOz1SK9H9nrkoMdX3Iytu11psiM_-vDA7Qgop1WRN6rS1h055hUmPfYwYL-2MIf_xsp0s03Xm23_BUDoHyMIe84</recordid><startdate>200009</startdate><enddate>200009</enddate><creator>Lamba, Jatinder K.</creator><creator>Dhiman, Radha K.</creator><creator>Kohli, Krishan K.</creator><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200009</creationdate><title>CYP2C19 genetic mutations in North Indians</title><author>Lamba, Jatinder K. ; Dhiman, Radha K. ; Kohli, Krishan K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3062-146a29651efb5926ce04153196bd4ea0e6e2ad72171ef2f0c0d3652f82c4c6a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Alleles</topic><topic>Antisense Elements (Genetics)</topic><topic>Aryl Hydrocarbon Hydroxylases</topic><topic>Biological and medical sciences</topic><topic>Cytochrome P-450 CYP2C19</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Female</topic><topic>General pharmacology</topic><topic>Genetics, Population</topic><topic>Genotype</topic><topic>Humans</topic><topic>India</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mixed Function Oxygenases - genetics</topic><topic>Omeprazole - metabolism</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenotype</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lamba, Jatinder K.</creatorcontrib><creatorcontrib>Dhiman, Radha K.</creatorcontrib><creatorcontrib>Kohli, Krishan K.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lamba, Jatinder K.</au><au>Dhiman, Radha K.</au><au>Kohli, Krishan K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CYP2C19 genetic mutations in North Indians</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2000-09</date><risdate>2000</risdate><volume>68</volume><issue>3</issue><spage>328</spage><epage>335</epage><pages>328-335</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><coden>CLPTAT</coden><abstract>Objectives
To identify defective alleles of CYP2C19 (CYP2C19*2 and *3) in North Indians.
Methods
One hundred extensive metabolizers and 21 poor metabolizers of omeprazole were genotyped with respect to CYP2C19*2 and *3 alleles with polymerase chain reaction–based diagnostic tests.
Results
Fifty‐two extensive metabolizers and six poor metabolizers were homozygous with the CYP2C19*1 /*1 genotype, and 48 extensive metabolizers and six poor metabolizers were heterozygous with the CYP2C19*1/*2 genotype. Nine poor metabolizers were homozygous with the CYP2C19*2/*2 genotype. No extensive or poor metabolizers demonstrated the presence of the CYP2C19*3 allele. CYP2C19*2 could explain 43% (9/21) of the poor metabolizers and 57% (24/42) of the defective alleles in poor metabolizers. Allele frequency of CYP2C19*1 and *2 was 0.7 (95% confidence interval of 0.65 to 0.75) and 0.3 (95% confidence interval of 0.25 to 0.35), respectively. Homozygous extensive metabolizers excreted 7.85 ± 7.6 μmol 5‐hydroxyomeprazole in 8 hours, which was 28% more as compared with heterozygous extensive metabolizers who excreted 5.6 ± 3.6 μmol 5‐hydroxyomeprazole in 8 hours (P < .05).
Conclusions
Cyp2C19*2 demonstrated allele frequency of 0.3, whereas CYP2C19*3 was absent in North Indians. Because CYP2C19*2 is not able to explain 57% of poor metabolizers, other mutations (CYP2C19*4 to *8) might be present in North Indians. CYP2C19 demonstrated differential evolution in North Indians because the frequency of CYP2C19*2 was similar to that in Oriental subjects, but that of CYP2C19*3 was similar to that in white subjects.
Clinical Pharmacology & Therapeutics (2000) 68, 328–335; doi: 10.1067/mcp.2000.109365</abstract><cop>New York, NY</cop><pub>Nature Publishing</pub><pmid>11014415</pmid><doi>10.1067/mcp.2000.109365</doi><tpages>8</tpages></addata></record> |
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| subjects | Alleles Antisense Elements (Genetics) Aryl Hydrocarbon Hydroxylases Biological and medical sciences Cytochrome P-450 CYP2C19 Cytochrome P-450 Enzyme System - genetics Female General pharmacology Genetics, Population Genotype Humans India Male Medical sciences Mixed Function Oxygenases - genetics Omeprazole - metabolism Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Phenotype Polymerase Chain Reaction Polymorphism, Genetic |
| title | CYP2C19 genetic mutations in North Indians |
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